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Rapid calcium-dependent activation of Aurora-A kinase
Plotnikova, Olga V. Pugacheva, Elena N.
Plotnikova, Olga V.
Pugacheva, Elena N.
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Journal article
Date
2010-09-07
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Department
Cancer and Cellular Biology
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http://dx.doi.org/10.1038/ncomms1061
Abstract
Oncogenic hyperactivation of the mitotic kinase Aurora-A (AurA) in cancer is associated with genomic instability. Increasing evidence indicates that AurA also regulates critical processes in normal interphase cells, but the source of such activity has been obscure. We report here that multiple stimuli causing release of Ca2+ from intracellular endoplasmic reticulum stores rapidly and transiently activate AurA, without requirement for second messengers. This activation is mediated by direct Ca2+-dependent calmodulin (CaM) binding to multiple motifs on AurA. On the basis of structure–function analysis and molecular modelling, we map two primary regions of CaM-AurA interaction to unfolded sequences in the AurA N- and C-termini. This unexpected mechanism for AurA activation provides a new context for evaluating the function of AurA and its inhibitors in normal and cancerous cells.
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Plotnikova OV, Pugacheva EN, Dunbrack RL Jr, Golemis EA. Rapid calcium-dependent activation of Aurora-A kinase. Nat Commun. 2010 Sep 7;1(64). doi:10.1038/ncomms1061.
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Nature Research
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Nature Communications, Vol. 1
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